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Biomedical subjects

Jeffrey S Hyams

Publications and source records attributed to Jeffrey S Hyams.

15 recordsLinked to original sources
PubMed2007

Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease.

BACKGROUND: In children with inflammatory bowel disease (IBD) it is not known whether reductions in bone mineral density (BMD) are a consequence of bone turnover alterations and if BMD improves with treatment. METHODS: In a cohort of children with IBD, we prospectively measured indicators of bone remodeling, body mass index (BMI), disease activity, intact parathyroid hormone, serum IL-6, and insulin-like growth factor-I at diagnosis and then every 6 months for 2 years. BMD was determined annually using dual x-ray absorptiometry (DXA). BMD Z-scores were calculated using height/age. Baseline measurements and calcium intake were compared with a group of age- and sex-matched healthy children. RESULTS: We observed that at diagnosis total body BMD Z-score (mean +/- SD) was -0.78 +/- 1.02 for Crohn's disease (CD, n = 58), -0.46 +/- 1.14 for ulcerative colitis (UC, n = 18), and -0.17 +/- 0.95 for control (CL, n = 49) (P < 0.01, CD versus CL). In CD, a BMD Z-score <-1.0 was associated with lower BMI and higher serum IL-6. Patients with CD and UC had low bone turnover. Activation of bone formation paralleled clinical improvement, but BMC gain was less than expected over the 2-year study period, especially in CD. Prednisone use did not correlate with low BMD. CONCLUSIONS: Decreased bone turnover occurs in children newly diagnosed with IBD. Although indicators of osteoblast activity increase with clinical improvement, bone mineral accrual does not accelerate. Children with low BMI may be considered for BMD screening, since they are at risk for low bone mass.

Absorptiometry, Photon↗
PubMed2006

Are activated T cells regulators of bone metabolism in children with Crohn disease?

OBJECTIVES: To test the hypothesis that circulating activated T cells may release cytokines that decrease bone turnover in children with Crohn disease. STUDY DESIGN: Newly diagnosed Crohn disease and healthy controls of similar age were compared for bone age, bone mineral content and density, markers of bone remodeling, and serum concentration and in vitro T-cell production of receptor activator of nuclear factor kappaB ligand (RANKL), interferon (INF)-gamma, and osteoprotegerin (OPG). RESULTS: Newly diagnosed children with Crohn disease (n=23) had similar bone mineral density (BMD) z-scores and body mass index as the controls (n=40). Biochemical markers of bone remodeling indicated a state of low bone turnover in the Crohn disease patients compared with controls. Serum OPG (pmol/L; mean+/-SD, median) was higher (4.24+/-1.74, 3.98 vs 3.38+/-0.83, 3.41; P<.05), and serum RANKL (pmol/L) was lower in the Crohn disease patients (0.50+/-0.86, 0.28 vs 1.02+/-1.63, 0.49; P<.01), consistent with decreased bone resorption. Activated T cells from Crohn disease patients produced a higher concentration of INF-gamma (ng/microg protein) than those from controls (20.03+/-26.39, 8.70 vs 9.76+/-14.10, 6.17; P<.05). CONCLUSIONS: The newly diagnosed children with Crohn disease exhibited reduced bone remodeling, possibly due to T-cell INF-gamma and OPG.

Adolescent↗
PubMed2006

Childhood functional gastrointestinal disorders: child/adolescent.

The Rome II pediatric criteria for functional gastrointestinal disorders (FGIDs) were defined in 1999 to be used as diagnostic tools and to advance empirical research. In this document, the Rome III Committee aimed to update and revise the pediatric criteria. The decision-making process to define Rome III criteria for children aged 4-18 years consisted of arriving at a consensus based on clinical experience and review of the literature. Whenever possible, changes in the criteria were evidence based. Otherwise, clinical experience was used when deemed necessary. Few publications addressing Rome II criteria were available to guide the committee. The clinical entities addressed include (1) cyclic vomiting syndrome, rumination, and aerophagia; 2) abdominal pain-related FGIDs including functional dyspepsia, irritable bowel syndrome, abdominal migraine, and functional abdominal pain; and (3) functional constipation and non-retentive fecal incontinence. Adolescent rumination and functional constipation are newly defined for this age group, and the previously designated functional fecal retention is now included in functional constipation. Other notable changes from Rome II to Rome III criteria include the decrease from 3 to 2 months in required symptom duration for noncyclic disorders and the modification of the criteria for functional abdominal pain. The Rome III child and adolescent criteria represent an evolution from Rome II and should prove useful for both clinicians and researchers dealing with childhood FGIDs. The future availability of additional evidence-based data will likely continue to modify pediatric criteria for FGIDs.

Abdominal Pain↗
PubMed2006

Challenges in pediatric inflammatory bowel disease.

It is estimated that of the >1 million individuals in the United States with inflammatory bowel disease (IBD), approximately 100,000 are children. IBD that begins in childhood affects the individual at a critical period of growth and development. Children with Crohn's disease and ulcerative colitis may experience complications such as growth failure, school absence, and depression. In addition, because children with IBD have fewer environmental confounders such as smoking, children may be an excellent population to study microbial and immune interactions. Despite these opportunities, the discipline of pediatric IBD investigation is still in its infancy. In September of 2005, a group of investigators with expertise in pediatric IBD met in Boston (Massachusetts) to review the current status of childhood IBD research and to develop research priorities that warranted funding from the Crohn's and Colitis Foundation of America. The group included pediatricians, internists, basic scientists, clinical investigators, and members of the administrative staff and board of the Crohn's and Colitis Foundation of America. The research needs in respective areas were outlined by the heads of 10 focus groups, each with expertise in their respective fields (genetics, psychosocial issues, epidemiology, microbiology, immunology, quality improvement, pharmacogenomics, nutrition, growth and skeletal health, and clinical trials). Before the conference, heads of the research focus groups developed their proposals with experts in the field. At the end of the conference, members of the focus groups and members of the steering committee rated the proposed areas of study in terms of feasibility and importance. It was recommended that the Crohn's and Colitis Foundation of America focus its initial efforts in pediatric IBD in 5 areas: the effects of inflammation on growth and skeletal development, the genetics of early-onset IBD, the development of quality improvement interventions to standardize and improve clinical care of children with IBD, the immunology of childhood IBD, and the diagnosis and treatment of psychosocial sequelae of childhood IBD. At the conclusion of the meeting, investigators discussed the formation of a multicenter collaborative network to advance clinical and basic research in the field.

Child↗
PubMed2005

Can we alter the natural history of Crohn disease in children?

The natural history of Crohn disease is characterized by recurrent bouts of active disease, the consequences of which can severely impair sufferers' physical and social functioning. Not only does the illness cause day-to-day morbidity for children but the consequence of the chronic inflammatory process also commonly results in the need for major intestinal surgery. The present challenge facing physicians treating children with Crohn disease is to alleviate symptoms and prolong periods of remission via the use of specifically targeted therapies while minimizing toxicity and promoting normal growth and development. Although systemic corticosteroids are effective in inducing clinical remission, they are of little or no benefit in maintaining remission and can contribute to linear growth retardation. Immunomodulating drugs such as azathioprine, 6-mercaptopurine and methotrexate have proved effective for inducing and maintaining remission of active Crohn disease. These agents are now commonly prescribed in children at diagnosis, after a severe attack or after surgery or in those who become corticosteroid-dependent or corticosteroid-resistant. Their use is not without potential adverse effects and not all patients respond well to these agents. With the introduction of biologic agents, notably the tumor necrosis factor-alpha monoclonal antibody infliximab, progress has been made in targeting specific pathogenetic mechanisms of Crohn disease and potentially altering the underlying disease process. Published experience in children is currently limited, but infliximab has been shown to improve symptoms and achieve corticosteroid independence in this age group. Unresolved issues with infliximab and other emerging biologic agents, including long-term safety, necessitate a degree of caution in selecting appropriate patients for treatment and with careful monitoring of their effects. The collection of contemporary natural history data is crucial to facilitate the better integration of current and emerging therapies in an attempt to alter the natural history of Crohn disease in children.

Adrenal Cortex Hormones↗
PubMed2005

Chronic Abdominal Pain In Children: a Technical Report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Chronic abdominal pain, defined as long-lasting intermittent or constant abdominal pain, is a common pediatric problem encountered by primary care physicians, medical subspecialists and surgical specialists. Chronic abdominal pain in children is usually functional-that is, without objective evidence of an underlying organic disorder. The Subcommittee on Chronic Abdominal Pain of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has prepared this report based on a comprehensive, systematic review and rating of the medical literature. This report accompanies a clinical report based on the literature review and expert opinion. The subcommittee examined the diagnostic and therapeutic value of a medical and psychologic history, diagnostic tests, and pharmacological and behavioral therapy. The presence of alarm symptoms or signs (such as weight loss, gastrointestinal bleeding, persistent fever, chronic severe diarrhea and significant vomiting) is associated with a higher prevalence of organic disease. There was insufficient evidence to state that the nature of the abdominal pain or the presence of associated symptoms (such as anorexia, nausea, headache and joint pain) can discriminate between functional and organic disorders. Although children with chronic abdominal pain and their parents are more often anxious or depressed, the presence of anxiety, depression, behavior problems or recent negative life events does not distinguish between functional and organic abdominal pain. Most children who are brought to the primary care physician's office for chronic abdominal pain are unlikely to require diagnostic testing. Pediatric studies of therapeutic interventions were examined and found to be limited or inconclusive.

Abdominal Pain↗
PubMed2005

Chronic abdominal pain in children: a clinical report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Children and adolescents with chronic abdominal pain pose unique challenges to their caregivers. Affected children and their families experience distress and anxiety that can interfere with their ability to perform regular daily activities. Although chronic abdominal pain in children is usually attributable to a functional disorder rather than to organic disease, numerous misconceptions, insufficient knowledge among health care professionals and inadequate application of knowledge may contribute to a lack of effective management. This clinical report accompanies a technical report on childhood chronic abdominal pain and provides guidance for the clinician in the evaluation and treatment of children with chronic abdominal pain. The conclusions are based on the evidence reviewed in the technical report and on consensus achieved among subcommittee members.

Abdominal Pain↗
PubMed2004

Irritable bowel syndrome, functional dyspepsia, and functional abdominal pain syndrome.

Recurrent or chronic abdominal pain is a description and not a diagnosis. The clinician should consider both disease and functional pain. In the absence of obvious disease, adolescents fulfilling symptom-based criteria for functional gastrointestinal disorders can be treated for their problems without initially performing extensive diagnostic studies. Most of these patients will have symptoms resembling IBS, functional dyspepsia, or functional abdominal pain syndrome. It is imperative that the clinician takes a biopsychosocial approach in dealing with these patients. Although the clinician still evaluates for biologic disease, he or she maintains an appreciation that psychosocial events may have a profound impact on physiology and symptom production.

Abdominal Pain↗
PubMed2002

Recurrent abdominal pain in children.

Functional abdominal pain can occur in a well-defined clinical entity (e.g., IBS) or as a part of a poorly defined clinical syndrome. Although the clinician may feel compelled to exclude disease in all cases, the authors suggest that it is more appropriate to take a biopsychosocial approach. In so doing, there can be an appreciation of the close interaction of the gut and the brain, allowing the child, family, and physician the opportunity to address the pain on many levels. Although the parameters set forth by the pediatric ROME II committee have facilitated the authors' description of these disorders greatly, basic research likely will further delineate biochemical processes in the enteric and central nervous systems that will expand therapeutic horizons.

Abdominal Pain↗
PubMed2002

Diet and gastrointestinal disease.

Dietary manipulation can be an important part of therapy for several common gastrointestinal disorders. In Crohn disease, the provision of adequate protein and calories may not only improve symptoms but may be associated with acceleration of growth. In celiac disease, the dietary restriction of gluten is curative of the intestinal inflammation. In chronic nonspecific diarrhea and functional constipation, the provision of appropriate amounts of fiber and fluids may ameliorate symptoms. A thorough understanding of the role of diet is essential to the management of these disorders.

Age Factors↗
PubMed2002

Effect of Crohn's disease on bone metabolism in vitro: a role for interleukin-6.

Circulating proinflammatory cytokines may be involved in osteopenia associated with Crohn's disease (CD). Therefore, the effect of interleukin (IL)-6, IL-1beta, and tumor necrosis factor (TNF) a contained in Crohn's serum on bone formation was examined in a bone organ culture system. Initially, serum levels of IL-6, IL-1beta, and TNF-a were determined by ELISA in newly diagnosed, untreated children with CD and healthy age-matched controls. Serum IL-6 levels were significantly higher in patients with CD than in controls (23.9 +/- 2.8 pg/ml vs. 0.7 pg/ml +/- 0.2; p < 0.001), whereas IL-1beta and TNF-alpha serum levels were not. In the organ culture studies, 20-day-old fetal rat parietal bones were incubated for 96 h with CD or control serum, serum preincubated with a neutralizing antibody to each cytokine or a nonimmune immunoglobulin control, and with IL-6. Bone formation measured by assaying calcium content and dry weight was significantly decreased in bones exposed to Crohn's serum. Light microscopy of the bones treated with CD serum revealed a discontinuous, uneven mineralized bone matrix and disorganized osteoblasts with altered morphology. Incubation with an antibody that neutralized IL-6 activity prevented the change in osteoblast and bone morphology. TNF-a and IL-1beta antibodies had no apparent effects. Collagen synthesis and DNA content were not affected by CD serum. Also, addition of IL-6 to the culture medium decreased mineralization. These results suggest that IL-6 is a mediator of the effects of Crohn's serum on in vitro mineralization and may be a contributing factor to the osteopenia associated with CD.

Adolescent↗